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UGT1A1 Gene Mutations in Pakistani Children Suffering from Inherited Nonhemolytic Unconjugated Hyperbilirubinemias

UGT1A1 Gene Mutations in Pakistani Children Suffering from Inherited Nonhemolytic Unconjugated... Two inherited unconjugated hyperbilirubinemias, Crigler–Najjar syndrome and Gilbert syndrome, arise due to deficiency of UGT1A1 enzyme activity. Crigler–Najjar syndrome type 1 (CN1) lies at the extreme severe end of the spectrum of UGT1A1 activity characterized by complete absence, followed by the less severe Crigler–Najjar syndrome type 2 (CN2). Gilbert syndrome is the mild form having only partial loss of UGT1A1 activity. The present study aimed to identify molecular genetic defects underlying unconjugated hyperbilirubinemias in children from six consanguineous Pakistani families. The patients were clinically diagnosed by exclusion of other unconjugated hyperbilirubinemias. Differential diagnosis of CN1 and CN2 was made on the basis of patient's response to phenobarbitone. The promoter region, coding exons, and adjacent splice sites of the UGT1A1 gene were PCR amplified from genomic DNA of all patients and their families, and were sequenced. DNA sequence analysis identified five different homozygous mutations: two novel missense mutations p.Y230C (proband A) and p.D36N (proband B), a 4‐bp insertion c.622–625dupCAGC/p.Q208QfsX50 (probands C and E), a nonsense mutation p.R341X (proband D), and a TA insertion A(TA)7TAA in the promoter region (proband F). The present study extends the spectrum of UGT1A1 gene mutations and may be helpful in the diagnosis of Crigler–Najjar syndrome and Gilbert syndrome. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Annals of Human Genetics Wiley

UGT1A1 Gene Mutations in Pakistani Children Suffering from Inherited Nonhemolytic Unconjugated Hyperbilirubinemias

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References (25)

Publisher
Wiley
Copyright
Copyright © 2013 John Wiley & Sons Ltd/University College London
ISSN
0003-4800
eISSN
1469-1809
DOI
10.1111/ahg.12039
pmid
23992562
Publisher site
See Article on Publisher Site

Abstract

Two inherited unconjugated hyperbilirubinemias, Crigler–Najjar syndrome and Gilbert syndrome, arise due to deficiency of UGT1A1 enzyme activity. Crigler–Najjar syndrome type 1 (CN1) lies at the extreme severe end of the spectrum of UGT1A1 activity characterized by complete absence, followed by the less severe Crigler–Najjar syndrome type 2 (CN2). Gilbert syndrome is the mild form having only partial loss of UGT1A1 activity. The present study aimed to identify molecular genetic defects underlying unconjugated hyperbilirubinemias in children from six consanguineous Pakistani families. The patients were clinically diagnosed by exclusion of other unconjugated hyperbilirubinemias. Differential diagnosis of CN1 and CN2 was made on the basis of patient's response to phenobarbitone. The promoter region, coding exons, and adjacent splice sites of the UGT1A1 gene were PCR amplified from genomic DNA of all patients and their families, and were sequenced. DNA sequence analysis identified five different homozygous mutations: two novel missense mutations p.Y230C (proband A) and p.D36N (proband B), a 4‐bp insertion c.622–625dupCAGC/p.Q208QfsX50 (probands C and E), a nonsense mutation p.R341X (proband D), and a TA insertion A(TA)7TAA in the promoter region (proband F). The present study extends the spectrum of UGT1A1 gene mutations and may be helpful in the diagnosis of Crigler–Najjar syndrome and Gilbert syndrome.

Journal

Annals of Human GeneticsWiley

Published: Jan 1, 2013

Keywords: ; ; ; ;

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